Research: SOX2 and SOX21 in Lung Epithelial Differentiation and Repair

Int J Mol Sci

. 2022 Oct 27;23(21):13064.

 doi: 10.3390/ijms232113064.

SOX2 and SOX21 in Lung Epithelial Differentiation and Repair

Evelien Eenjes 1Dick Tibboel 1Rene M H Wijnen 1Johannes Marco Schnater 1Robbert J Rottier 1 2

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Free PMC article


The lung originates from the ventral foregut and develops into an intricate branched structure of airways, alveoli, vessels and support tissue. As the lung develops, cells become specified and differentiate into the various cell lineages. This process is controlled by specific transcription factors, such as the SRY-related HMG-box genes SOX2 and SOX21, that are activated or repressed through intrinsic and extrinsic signals. Disturbances in any of these processes during the development of the lung may lead to various pediatric lung disorders, such as Congenital Diaphragmatic Hernia (CDH), Congenital Pulmonary Airway Malformation (CPAM) and Broncho-Pulmonary Dysplasia (BPD). Changes in the composition of the airways and the alveoli may result in reduced respiratory function and eventually lead to chronic lung disorders. In this concise review, we describe different intrinsic and extrinsic cellular processes required for proper differentiation of the epithelium during development and regeneration, and the influence of the microenvironment on this process with special focus on SOX2 and SOX21.

Keywords: SOX proteins; lung development; lung stem cells; regeneration.

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